Stability of the nitrogen mustard mechlorethamine in novel formulations for dermatological use

Long term stability measurements were made for the nitrogen mustard mechlorethamine HCl at a concentration of 0.02% in six topical formulations: Aquaphor® ointment, Transcutol®, Labrasol®, 10% Transcutol® in Aquaphor®, 10% Transcutol® in Labrasol®, and Aquaphilic® ointment. The drug decomposed gradually in Aquaphor® ointment at room temperature, dropping to 95% in 4 weeks, 85% in 12 weeks, and 78% in 39 weeks. On the other hand, the drug decomposed rapidly in Aquaphilic® ointment, giving an assay of less than 20% of its initial concentration after 24h at room temperature. Generally, mechlorethamine HCl was more stable in Aquaphor® ointment than in formulations containing Transcutol® or Labrasol®. However, the addition of the free radical inhibitor, BHT, significantly enhanced the stability of mechlorethamine in Transcutol® and Labrasol® formulations. Four BHT-stabilized Transcutol® and Labrasol® formulations gave assays in ranges of 92–99% at the end of 4 weeks, 77–98% at the end of 12 weeks, and 38–93% at the end of 41 weeks.